Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.

Supramolecular gels, which demonstrate tunable functionalities, have attracted much interest in a range of areas, including healthcare, environmental protection and energy-related technologies. Preparing these materials in a reliable manner is challenging, with an increased level of kinetic defects observed at higher self-assembly rates. Here, by combining biocatalysis and molecular self-assembly, we have shown the ability to more quickly access higher-ordered structures. By simply increasing enzyme concentration, supramolecular order expressed at molecular, nano-and micro-levels is dramatically enhanced, and, importantly, the gelator concentrations remain identical. Amphiphile molecules were prepared by attaching an aromatic moiety to a dipeptide backbone capped with a methyl ester. Their self-assembly was induced by an enzyme that hydrolysed the ester. Different enzyme concentrations altered the catalytic activity and size of the enzyme clusters, affecting their mobility. This allowed structurally diverse materials that represent local minima in the free energy landscape to be accessed based on a single gelator structure.M olecular self-assembly 1-7 can be controlled using a variety of stimuli, including chemical 8,9 and mechanical 10 triggers, as well as X-rays 11 . Although the traditional premise in selfassembly suggests that supramolecular material properties can be fully encoded into molecular building blocks, it is increasingly apparent that the chosen self-assembly pathway is central to the final structure and its material functionality. Biocatalytic control of self-assembly systems is a novel direction for laboratory-based self-assembly 12-17 , although it is omnipresent in the biological world. Indeed, enzymatically controlled self-assembly and disassembly underlies vital processes such as cell movement, intracellular transport and muscle contraction. In chemists' hands, the combination of biocatalysis and molecular self-assembly has recently emerged as a powerful new approach to make novel stimuli-responsive molecular materials [12][13][14][15][16][17] . We believe that catalytic control of self-assembly provides important new methodology beyond such triggering of material transitions. In particular, the combination of biological selectivity, localized action and operation under constant, physiological conditions provides a new methodology for bottomup nanofabrication of future soft materials and devices, allowing for unprecedented control of supramolecular order.Here, we focus on the control of supramolecular order with few defects. In principle, there are two possible approaches to defect reduction-either improving the fidelity of the self-assembly process (avoiding defects) or using fully reversible systems that operate under thermodynamic control (repairing defects). The latter approach is generally slow and only applicable to cases where the desired structure represents the global equilibrium state and where the system is fully reversible, that is, under thermodynamic control 16 . Many structure...

Several short peptide sequences are known to self-assemble into supramolecular nanostructures with interesting properties. In this study, coarse-grained molecular dynamics is employed to rapidly screen all 400 dipeptide combinations and predict their ability to aggregate as a potential precursor to their self-assembly. The simulation protocol and scoring method proposed allows a rapid determination of whether a given peptide sequence is likely to aggregate (an indicator for the ability to self-assemble) under aqueous conditions. Systems that show strong aggregation tendencies in the initial screening are selected for longer simulations, which result in good agreement with the known self-assembly or aggregation of dipeptides reported in the literature. Our extended simulations of the diphenylalanine system show that the coarse-grain model is able to reproduce salient features of nanoscale systems and provide insight into the self-assembly process for this system.

Abstract. Stem cells are known to differentiate in response toHowever, identification of these stem cell inducing molecules is non-trivial and rational approaches to discover drugs for achieving reproducible, targeted stem cell control remain elusive. Here, we demonstrate the design of supramolecular hydrogels that allow targeting of a range of stem cell phenotypes, providing a useful platform for discovery of differentiation inducing metabolites. These gels are simple in composition, containing a fibre forming aromatic peptide amphiphile, which is coassembled with a surfactant-like amphiphile that provides hydrophilic surface functionality to the fibres. The stiffness of the gels can be precisely tuned over the entire range that is typically associated with stem cell differentiation (0.1-40 kPa). 3We demonstrate that the gels can be used to direct stem cell differentiation without the need for induction media and they are therefore ideally suited to study stem cell behaviour -including as drug discovery platforms. To achieve this, we study the cell's usage of biological small molecules, metabolites, during differentiation and select bioactive metabolites that can target bone and cartilage formation specifically. This new use of designed supramolecular biomaterials can be envisaged to remove serendipity from discovery of metabolites associated with biological processes as drug candidates. Introduction.

β-Sheets are a commonly found structural motif in self-assembling aromatic peptide amphiphiles, and their characteristic "amide I" infrared (IR) absorption bands are routinely used to support the formation of supramolecular structure. In this paper, we assess the utility of IR spectroscopy as a structural diagnostic tool for this class of self-assembling systems. Using 9-fluorene-methyloxycarbonyl dialanine (Fmoc-AA) and the analogous 9-fluorene-methylcarbonyl dialanine (Fmc-AA) as examples, we show that the origin of the band around 1680-1695 cm(-1) in Fourier transform infrared (FTIR) spectra, which was previously assigned to an antiparallel β-sheet conformation, is in fact absorption of the stacked carbamate group in Fmoc-peptides. IR spectra from (13)C-labeled samples support our conclusions. In addition, DFT frequency calculations on small stacks of aromatic peptides help to rationalize these results in terms of the individual vibrational modes.